tbuckley/cabot-search huggingface dataset:
Abstract 14592: Impact of Sodium Abnormalities: Hypernatremia vs Hyponatremia on Inpatient Hospital Congestive Heart Failure Outcomes: A National Inpatient Sample Data Analysis
Authors: Pradeep kumar Devarakonda, Sohrab Singh, monika karki, Akshaya Gopalakrishnan, Vishal Dhulipala, Lalitsiri Atti, Suganya Manoharan, Linus Yoe, Praneeth Bandaru, Sarath Reddy
Journal: Circulation (2022)

Introduction Sodium abnormalities are commonly associated with congestive heart failure (CHF). The main objective of this study is to analyze the impact of hyponatremia vs. hypernatremia on in-hospital outcomes in patients admitted with CHF Methods The National inpatient sample (NIS) data from 2017 to 2018 were queried using International Classification of Diseases 10 (ICD-10-CM) codes E871 and E870. Demographics and hospital characteristics were compared along with In-hospital mortality, length of stay (LOS), and total charge. The outcomes were measured using linear and logistic regression models to adjust the odds ratio for confounders. Results: A total of 350,144 patients with heart failure as a primary diagnosis (42% systolic and 32% diastolic HF) were included in the study. Among them, 37,129 (10.7%) had hyponatremia while 5839 (1.8%) had hypernatremia. In-hospital mortality rates were significantly higher with an adjusted odds ratio (OR) of 2.78 (p&lt;0.001) among hypernatremia patients. Mean length of stay (LOS) was also high among hypernatremia patients (12.3 vs 8 days), with an adjusted odds ratio of 4.89 (p-value &lt;0.001). Similarly, mean total charges were higher in the hypernatremia group (175,632$ vs 91,022 $). Notably, hypernatremia was associated with more hemorrhage complications (OR-6.35, p &lt;0.001). Conclusions: Even though hypernatremia is less frequent than hyponatremia among CHF patients, it is associated with significantly higher mortality, LOS, and total charges than hyponatremia.
Abstract 15316: Associations Between Plasma Proteins With Body Composition Traits and Their Responses to Exercise Training
Authors: William A Clarkson, Jacob L Barber, Jeremy M Robbins, Guoshuai Cai, Prashant Rao, Michael Mi, Prasun Dev, Sujoy Ghosh, Daniel H Katz, Clary Clish, Claude Bouchard, Mark A Sarzynski, Robert E Gerszten
Journal: Circulation (2022)

Introduction: Although exercise training is known to alter body composition, the molecular biomarkers and mechanisms related to these changes have not been fully elucidated. The purpose of this study was to examine the associations between plasma proteins and body composition traits before and after exercise training. Methods: Measurements were taken before and after 20 weeks of standardized, endurance training in self-identified Black and White adults of the HERITAGE Family Study (n=647). Plasma proteins were measured using an affinity-based platform (n=4979 aptamers). 11 body composition traits were measured using underwater weighing, CT scans, and anthropometry: BMI, body surface area, fat mass, fat free mass, %fat, waist circumference, waist-to-hip ratio, body weight, and abdominal visceral, subcutaneous, and total fat. Linear mixed models were used to test the association between plasma proteins and each trait at baseline and in response to training with full covariate adjustment ( Table 1 ). Significance was set to FDR&lt;0.05. Results: On average, subjects were [mean and (SD)] 35 (14) years old, 33% Black, 54% female, and had BMI 26.2 (5.2) kg/m 2 . The number of significant associations between proteins and traits at baseline and in response to exercise training ranged from 645-1714 and 0-42, respectively ( Table 1 ). While leptin was among the top associated proteins at both time points for almost all traits, our analysis revealed many novel associations between changes in proteins with changes in body composition. Changes in DLK-1 significantly associated with changes in 9 of 11 traits but was not associated with baseline measures. Conclusions: Numerous plasma proteins were associated with body composition traits at baseline, with fewer associated with trait responses to training. Notably, we identified a subset of proteins uniquely associated with exercise-induced changes in body composition traits.
Abstract 14434: Prognostic Implications of Exercise Induced Hypertension in Adults With Repaired Coarctation of Aorta
Authors: Dhanya Ramachandran, Kartik Andi, Ahmed Goda, OMAR ABOZIED, Alexander C Egbe
Journal: Circulation (2022)

Background: The prognostic implications of exercise induced hypertension (EIH) in adults with repaired coarctation of aorta (COA) and treated hypertension are unknown. The purpose of this study was to assess the relationship between EIH and cardiovascular events, and to determine whether exercise blood pressure (BP) improved risk stratification in this population. Methods: Retrospective study of patients with COA on antihypertensive therapy that underwent exercise testing (2003-2019). BP was measured at rest in 3 different clinical settings and averaged to determine the resting BP. EIH was defined as systolic BP (SBP) &gt;210 (males) or &gt;190 (females) at peak exercise. Cardiovascular event was defined as atrial fibrillation, ventricular tachycardia, heart failure hospitalization, heart transplant, and cardiovascular death. Results: Of 327 patients (age 35±13 years), 116 (35%) had EIH. Although the resting BP was similar between patients with versus without EIH, the EIH group had higher pulsatile arterial load, more advanced left ventricular remodeling, and were less likely to be on angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB). EIH was associated with cardiovascular events (HR 1.06 [95%CI 1.02-1.08]) independent of resting SBP, and improved prognostic accuracy above resting SBP (C-statistic 0.671 [95%CI 0.645-0.694] to 0.727 [95%CI 0.709-0.750], p=0.01). ACEI/ARB was associated with a lower risk of cardiovascular events. Conclusions: EIH was associated with cardiovascular events independent of resting BP, and patients receiving ACEI/ARB had lower risk of EIH and cardiovascular events. These data suggest that exercise BP could be used to assess adequacy of antihypertensive therapy, and to guide titration of antihypertensive therapy.
Abstract 14712: PCI is Safe and Increasing Among Cancer Patients: Nationally Representative Propensity Score Adjusted and Machine Learning Augmented Study of 100 Million Hospitalizations
Authors: Bala Pushparaji, Dominique Monlezun, Nicolas L Palaskas, Efstratios Koutroumpakis, Konstantinos D Boudoulas, Abhijeet Dhoble, Konstantinos Marmagkiolis, Cezar Iliescu
Journal: Circulation (2022)

Introduction: The greater use of antithrombotic and antiplatelet agents in the growing population of patients with cardiovascular disease and cancer contrasts with the limited evidence-base on appropriate revascularization management for these patients. Methods: This is the first nationally representative multi-year cardio-oncology mortality study of thrombocytopenia (platelets &lt;150,000) and coronary intervention including percutaneous coronary intervention (PCI), and the first such study using machine learning augmentation and propensity score (PS). Utilizing the 2016-2018 National Inpatient Sample (NIS), the PS for receiving PCI was generated, balance confirmed, and regression adjustment completed (also including age, sex, race, income, urban, region, metastasis, NIS-calculated mortality risk by disease-related group), and multivariable regression model performance was optimized using backward propagation neural networks. Results: Of the 101,521,656 hospitalized adult patients, 6,456,777 (6.36%) had active cancer of whom 6.14% had thrombocytopenia. Among thrombocytopenia patients, patients with versus without active cancer were significantly (p&lt;0.001) less likely to receive left heart catheterization (1.88 vs. 5.41%) and PCI (0.48 vs. 1.35%). Among cancer patients, patients with versus without thrombocytopenia were more likely to have acute myocardial infarction (4.06 vs. 2.35%) and to receive intravascular ultrasound (62.65 vs. 56.75%) but had comparable rates of fractional flow reserve and optical coherence tomography. PCI nearly doubled from 2016 to 2018 among patients with thrombocytopenia (10.33 vs. 6.16%). In multivariable regression in PCI, neither active cancer (OR 0.89, 95%CI 0.45-1.75; p=0.738) nor any of the 32 tested primary malignancies significantly increased mortality. Conclusions: This nationally representative longitudinal study suggests inpatient PCI is safe and is increasing among patients with active cancer regardless of their primary malignancy.
Abstract 13151: Left Ventricular Hypovolemia Secondary to in Utero Mitral Valve Inflow Obstruction in a Late-Gestation Fetal Lamb Model
Authors: Daisuke Onohara, Matthew Hagen, Samantha Louey, George Giraud, Sonnet Jonker, Muralidhar Padala
Journal: Circulation (2022)

Introduction: Hypoplastic left heart syndrome (HLHS) is a congenital heart defect of an underdeveloped left ventricle (LV), necessitating palliative interventions after birth to survive. HLHS often occurs alongside mitral or aortic valve stenosis, lending to the hypothesis that reduced blood flow into and out of the LV in utero could retard LV growth. We have developed a late-gestation fetal lamb model to investigate if in utero mitral inflow obstruction could cause LV hypovolemia. Methods: Twelve pregnant ewes with twin fetuses at 82% gestation were used. In the experimental fetuses (EXPT), mitral inflow obstruction was achieved with an inflatable balloon catheter implanted into the left atrium (LA) in a beating heart. Other implants included a flow probe on the ascending aorta to measure cardiac output, and carotid artery and jugular vein catheters to monitor fetal health. After recovery from surgery, progressive LA balloon inflation began at ~86% gestation, and was left inflated for 8 days (92% gestation). Transesophageal fetal ultrasound was performed at baseline and at termination to measure cardiac chamber volumes and function. Hearts were explanted, weighed and prepared for histology. Results: Fetal body weights were similar (EXPT: 4.6±0.9kg vs CTRL: 4.5±0.6kg, p=0.8597). Total heart weight was higher in EXPT (31.4±5.6g) than CTRL (26.4±2.4g, p=0.0471), but LV weight was similar (EXPT: 7.4± 1.8g vs. CTRL: 7.9± 1.1g, p=0.5652). LV end-diastolic volume was 2.3± 0.7ml in EXPT vs. 7.1± 0.8ml in CTRL (p&lt;0.0001), and end-systolic volume was 1.01ml (0.95 to 1.95ml) in EXPT vs. 3.38ml (3.28 to 3.57ml) in CTRL (p=0.0025). LV/RV weight ratio was 0.83±0.17 in EXPT and 1.08±0.19 in CTRL (p=0.0209), whereas LV/RV chamber area ratio was 0.21±0.06 in EXPT and 0.56±0.05 in CTRL (p=0.0005). Conclusions: In this fetal sheep model, obstructing mitral inflow retarded LV growth, demonstrating a potential mechanistic link between blood inflow and in utero LV volumetric growth.
Abstract 15504: High-Throughput Assessment of Molecular Mechanisms of Drug-Induced Arrhythmia Proclivities and Their Sex Dependence
Authors: Kyle C Rouen, Khoa Ngo, Abhishek Kognole, John Dawson, Aiyana Emigh, Slava Bekker, Vladimir Yarov-Yarovoy, Alexander D MacKerell, Igor Vorobyov
Journal: Circulation (2022)

Introduction: The hERG K + channel is responsible for the repolarizing cardiac current I Kr . Drug block of hERG can prolong the QT interval on the surface electrocardiogram and in some cases promote deadly arrhythmias. Previous studies suggested that drugs that preferentially bind to the hERG channel’s inactivated state have higher proarrhythmic proclivities. Electrophysiology experiments and multiscale simulations also predicted that sex hormones can suppress hERG current and exacerbate drug-induced cardiotoxicity. Hypothesis: Atomistic simulations can make reliable correlations between a drug’s chemical structure and its state-dependent hERG binding affinities allowing us to distinguish safe from dangerous hERG blockers. Methods: We utilized site identification by ligand competitive saturation (SILCS), a pre-compute ensemble molecular docking technique, to predict hERG-channel binding poses and affinities of drug molecules. To improve agreement of SILCS results with experimental and molecular dynamics simulation data, we used a Bayesian machine learning protocol to optimize docking parameters. Results: We analyzed state-dependent binding of a sample set of 55 known hERG blockers and seven sex hormones to available structural models of the hERG channel. SILCS computed dissociation constants, K D , show good correlation with experimental IC 50 values for our open-state model (Panel A) and predict drug and hormone binding sites in agreement with previous studies (Panel B) validating the methodology. Conclusions: Our computational methodology allows us to do high-throughput screening and differentiation of open vs. inactivated-state hERG channel drug binding and can also predict how hormones may modulate a drug’s hERG blocking activity. This provides more selective criteria for differentiating cardiac safe and dangerous drugs compared to using only hERG block and QT prolongation as surrogate markers of pro-arrhythmia risk.
Abstract 15810: Cerebral Thrombus Transcriptome in Acute Ischemic Stroke
Authors: Emma M Federico, Christopher Dupont, Alexandra Gonzalez, Michael Levitt, Melanie Walker
Journal: Circulation (2022)

Establishment of mechanical thrombectomy as the standard of care provides a unique opportunity to refine stroke subtype mechanism by studying thrombus retrieved from stroke patients. Using traditional pathologic methods, researchers have described the form and structure of cerebral thrombi. These methods do not spatially resolve tissues and cell populations with functional segmentation. We applied next generation genomic tools to determine the spatially resolved transcriptome within cerebral thrombus. Methods: Cerebral thrombus was retrieved under sterile conditions. Tissue was formalin-fixed and paraffin embedded in standard fashion. Using the GeoMx Digital Spatial Profiling platform, morphology marker antibodies and WTA RNA probes coupled to photocleavable oligonucleotide tags were applied to the slide. After hybridization of the probes to tissue sections, 24 regions of interest (ROIs) were selected, and oligonucleotide tags were released from the discrete regions of the tissue via UV exposure. Released tags were quantitated using next generation sequencing and counts were mapped back to tissue location, yielding a spatially-resolved digital profile of analyte abundance. Results: Sequencing quality was inspected for sufficient saturation and data normalized to the third quartile to account for differences in cellularity. 18,676 genes were assayed across the 24 ROI. Of these, 4,590 genes were expressed in 10% of ROI and 1,127 genes were expressed in 50% of ROI. Conclusion: Significant transcriptional activity is seen within cerebral thrombus and preliminary analysis shows feasibility for a novel application of spatial transcriptomics. Further evaluation of expressed genes provides information about the microenvironment of thrombus origin and mechanistic insight to stroke subtype etiology. Figure. Number of genes detected across increasing % of ROIs.
Abstract 15256: Treatment With Ketone Ester in Patients With Cardiogenic Shock Improves Cardiac Performance
Authors: Kristoffer Berg Hansen, Kristian Hylleberg Christensen, Nigopan Gopalasingam, Roni Nielsen, Niels Møller, Thomas Birkelund, steffen christensen, Henrik Wiggers
Journal: Circulation (2022)

Introduction: Cardiogenic shock is a life-threatening condition but no medical therapy has been documented to improve outcome. Recent evidence suggests that the ketone body 3-hydroxybutyrate (3-OHB) has favorable hemodynamic effects in patients with stable chronic heart failure. However, the hemodynamic effects of exogenous ketone supplements to patients with cardiogenic shock remains unknown. Hypothesis: In patients hospitalized with cardiogenic shock, acute treatment with a ketone ester has beneficial hemodynamic effects. Methods: In a randomized, double-blind, crossover study, we included 12 patients with cardiogenic shock who were treated with inotropes and/or vasopressors. In random order, patients received an enteral bolus of 500 mg/kg ketone ester (KetoneAid Inc.) and isocaloric, isovolemic placebo containing maltodextrin. Each study period lasted for three hours and was separated by a 3-hour washout period. The primary endpoint was change in cardiac output expressed as area under curve (AUC). Secondary endpoints were recorded at the end of each study period and included mixed venous saturation (SVO 2 ), pulmonary capillary wedge pressure, and echocardiographic measures of contractile function. Results: The ketone ester increased circulating 3-OHB significantly vs. placebo (peak: 3.7±0.5 mmol/L vs. 0.3±0.1 mmol/L, AUC: 6.0±0.9 mmol/L x hour vs. 0.3±0.1 mmol/L x hour, all p&lt;0.001). This was accompanied by an increase in cardiac output (5.1±0.3 L/min vs. 4.4±0.3 L/min, p=0.043; AUC of relative change: 61±22 L vs. 1±18 L, p=0.044), primarily due to a higher stroke volume (53±4 mL vs. 47±4 mL, p=0.048). Ketone ester increased SVO 2 vs. placebo (61±2% vs. 57±3%, p=0.035) whereas heart rate, mean arterial, pulmonary arterial, and pulmonary capillary wedge pressures did not differ between study periods. Ketone ester increased left ventricular ejection fraction (32±3% vs. 28±3%, p=0.005) and global longitudinal strain (-7.3±0.7% vs. -6.5±0.6%, p=0.01) as compared with placebo. Conclusions: Treatment with ketone ester has beneficial hemodynamic effects in patients with cardiogenic shock by increasing cardiac output and left ventricular function.
Abstract 14626: Dissecting Out Risk Factors: A Case of Spontaneous Coronary Artery Dissection Without Traditional Risk Factors, in the Presence of Methamphetamine Use
Authors: Mohammed Ali, Todd Nagamine, Witina Techasatian, Maan Kathryn Gozun, Parthav Shah, Jason Kuniyoshi, Kevin Benavente, James Zhang, Jihun Yeo, Dipanjan Banerjee
Journal: Circulation (2022)

Introduction: Methamphetamine use is not a traditional risk factor for spontaneous coronary artery dissection (SCAD). There have been several case reports suggesting an association between methamphetamine use and SCAD. Case: We present a case of a 50-year-old female with a history of hypertension, hyperlipidemia, stroke, and active tobacco use who presented with substernal chest pain radiating to the back and abdomen with associated dyspnea and diaphoresis. The patient was also taking warfarin for a prior history of deep venous thrombosis. Her serum 5 th generation troponin level was elevated to a peak of 1135 ng/L, and a 12-lead EKG showed ST-elevations not meeting STEMI criteria (1mm in V3, 2mm in V4, and 0.5mm in V5). Coronary angiography showed a short section of SCAD type 1 involving the mid portion of the LAD with TIMI 3 flow. There was no significant atherosclerotic disease throughout any of the vessels. The patient was managed conservatively with medical therapy and had resolution of her pain. CT-angiography of the chest, abdomen and pelvis was performed to rule out dissection involving the aorta and its branches and was unrevealing. Urine toxicology screening returned positive for methamphetamine. Given a lack of other traditional risk factors aside from gender, the patient was diagnosed with SCAD secondary to methamphetamine use. Discussion: Traditional risk factors for SCAD include female sex, fibromuscular dysplasia, connective tissue disease, multiparity (our patient was parity 1), and exogenous hormone use. Methamphetamine use as well as prescription amphetamines have been associated with SCAD in several case reports. SCAD tends to occur in women with an absence of risk factors for coronary artery disease. However, even in patients with multiple risk factors for atherosclerosis and an absence of risk factors for SCAD, SCAD should not be excluded in the differential when a history of amphetamine use is elicited.
Abstract 14493: Strength- and Aerobic-Based Cardiac Rehabilitation Improves Intermediate Outcomes and Functional Capacity in Patients With Diabetes
Authors: Nina Liu, Anthony Khong, Elizabeth Cortez-Toledo, Humberto Andrade, Jose Gonzalez Tinoco, margaret junker, Javier E Lopez
Journal: Circulation (2022)

Background: Improvement in cardiorespiratory fitness during comprehensive cardiac rehabilitation (CR) is associated with improved cardiovascular prognosis. However, data on the improvement of intermediate outcomes (IOs) also associated with improved prognosis, i.e., low density lipoprotein (LDL) cholesterol and systolic blood pressure (SBP), in patients living with diabetes (DM) has been conflicting. The aim of this study is to characterize the integrated effects of combining strength and aerobic training on these IOs and functional capacity for patients living with and without DM. Methods: We retrospectively reviewed 377 CR program enrollments from 333 individual patients from 12/2019 - 3/2022. Paired functional capacity was assessed by the metabolic equivalent of task (METs) in a 6-minute walk test (6-MWT), arm curl reps, chair-to-stand reps, and timed up and go test. Demographics and IOs were obtained from the electronic records. P-values were determined by the Chi-square test for categorical variables and Mann-Whitney U test for continuous variables. Results: Baseline demographics and comorbidities of our cohort are described in Table 1. Patients with DM had more CAD and CKD. All patients undergoing CR showed integrated improvements in LDL with functional capacity in this paired analysis. However, patients without DM demonstrated a more significant reduction in SBP (Table 2). Conclusions: Combining strength and aerobic training resulted in integrated improvements in lipids and functional outcomes between patients with and without DM. Our results highlight the efficacy of this combined training for all CR patients, and the need for closer monitoring and management of SBP, a critical disease driver in patients with DM, CAD, and CKD.
Abstract 14500: Association Between the Arrival Time of Paramedics and the Neurological Outcome at Discharge of Cardiac Arrest Patients
Authors: Kichan Han, Seung Min Park
Journal: Circulation (2022)

Introduction: Improving survival rate and neurological outcome of out-of-hospital cardiac arrest (OHCA) patients is a global public health challenge. Prompt and appropriate management by emergency medical service at the prehospital stage is essential to achieve a good outcome in OHCA patients. Hypothesis We hypothesized that the arrival time of the second ambulance may affect the prognosis of patients with cardiac arrest, and this study aimed to investigate the relationship between the arrival time of last-arrival ambulance and the neurological outcome at discharge. Methods This study was a retrospective analysis of a prospectively collected registry of OHCA patients. Adult non-traumatic OHCA patients from Jan 2017 to Dec 2018 were included. ROC analysis was performed for good neurological outcomes, according to the arrival time of the last-arrival ambulance. Comparing the early arrival team (response time of last-arrival ambulance less than 14 minutes) and the late arrival team (response time of last-arrival ambulance 14 minutes or longer) with propensity score matching. Results A total 3,289 OHCA patients from 12 cities of Gyeonggi province, metropolitan area located in the suburbs of the capital of Republic of Korea was included. optimal cut off was 14 minutes. After propensity score matching, Survival to admission, survival discharge and good neurological outcome were higher in the early arrival team than the late arrival team [26.1% versus 21.3, 12.6% versus 6.3% and 7.1% versus 3.2%]. The response time of last-arrival team 14-minute or longer group showed a significant association with poor neurological outcomes at discharge compared to the group with less than 14 minutes [Odds ratio 2.87, 95% confidence interval 1.65-5.11, P value &lt; 0.001]. Conclusion In two-tier ambulance system, response time of last-arrival team 14-minute or longer was associated with poor neurological outcomes upon discharge in out-of-hospital cardiac arrest patients.